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BACKGROUND: Testosterone therapy (TTh) is recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD); however, there remain insufficient data to support use of TTh in premenopausal women with sexual dysfunction. AIM: In this study, we used a large national database to evaluate prescribing trends of TTh for women with HSDD. METHODS: We conducted a cohort analysis of information from electronic health records acquired from the data network TriNetX Diamond. The study cohort consisted of women 18-70 years of age with a diagnosis of HSDD. We analyzed trends of testosterone prescriptions, routes of testosterone administration, and coadministration of testosterone with estrogen. OUTCOMES: Despite an increase in rates of testosterone prescriptions for HSDD, there remains a high degree of variability in the duration of treatment, route of administration, and coadministration of estrogen with significant underprescription of testosterone. RESULTS: Our query of the TriNetX database led to the identification of 33 418 women diagnosed with HSDD at a mean age of 44.2 ± 10.8 years, among whom 850 (2.54%) women received a testosterone prescription. The testosterone prescriptions were highly variable with regard to duration and route of administration and coadministration with estrogen. For all patients until 2015, the prevalence of testosterone prescriptions for HSDD showed a positive quadratic relation was observed. Since 2015 a linear increase in prevalence was observed, with the highest rate of increase for patients aged 41-55 years. CLINICAL IMPLICATIONS: The findings of this study reveal a significant need for further research investigating the optimal use of TTh to enhance the sexual health of women with HSDD, and further studies on the long-term effects of testosterone use must be undertaken to ensure that patients have access to safe and effective treatment. STRENGTHS AND LIMITATIONS: Limitations to this study include patient de-identification and lack of availability of testosterone dosage data. However, this study also has many strengths, including being the first, to our knowledge, to characterize the prescribing trends of testosterone for women with HSDD. CONCLUSION: Testosterone therapy should be considered as a potential therapy for premenopausal female patients with HSDD. Further studies on the long-term effects of testosterone use must be undertaken to address disparities in the management of HSDD and to ensure patients can access treatment.
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Disfunciones Sexuales Fisiológicas , Disfunciones Sexuales Psicológicas , Adolescente , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Estrógenos/uso terapéutico , Libido , Premenopausia , Disfunciones Sexuales Fisiológicas/inducido químicamente , Disfunciones Sexuales Psicológicas/tratamiento farmacológico , Disfunciones Sexuales Psicológicas/epidemiología , Disfunciones Sexuales Psicológicas/diagnóstico , TestosteronaRESUMEN
OBJECTIVES: To characterise the outcomes of neoadjuvant chemotherapy (NAC) pre-treated patients found to be lymph node (LN)-positive at the time of radical cystectomy and pelvic lymph node dissection (RC/PLND) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Of 1484 patients treated with RC/PLND for UCB from 2000 to 2010, we analysed 198 patients with clinically non-metastatic (cN0M0) muscle-invasive UCB who were found to be LN-positive at RC/PLND. As patients not receiving perioperative chemotherapy were significantly older and comorbid, we compared LN-positive patients previously treated with NAC (32 patients) to LN-positive patients treated with adjuvant chemotherapy (AC, 49 patients) using Cox proportional hazards models. A sensitivity analysis was designed to account for the additional time to RC in NAC patients. RESULTS: The 3-year recurrence-free survival estimate for LN-positive NAC patients was 26%, compared with 60% for LN-positive AC patients. LN-positive patients treated with NAC had significantly higher risks of disease recurrence and cancer-specific mortality in univariate analyses (hazard ratio [HR] 2.86, 95% confidence interval [CI] 1.58-5.19, P = 0.001 and HR 2.50, 95% CI 1.34-4.65, P = 0.004, respectively) and multivariable analyses adjusting for pathological stage and LN density (HR 3.11, 95% CI 1.59-6.07, P = 0.001 and HR 3.05, 95% CI 1.46-6.35, P = 0.003, respectively). Sensitivity analyses similarly demonstrated worse outcomes for NAC pre-treated LN-positive patients. CONCLUSION: LN-positive patients previously treated with NAC have a poor prognosis, significantly worse than LN-positive patients subsequently treated with AC, and should be considered for protocols using sandwich chemotherapy approaches or novel agents. These results should be considered in the interpretation of and stratification for clinical trials.
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Ganglios Linfáticos/patología , Metástasis Linfática/patología , Terapia Neoadyuvante/estadística & datos numéricos , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Cistectomía , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
PURPOSE: Parastomal hernia is a frequent complication of stoma formation after radical cystectomy. We determined the prevalence and risk factors for the development of parastomal hernia after radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective study of 433 consecutive patients who underwent open radical cystectomy and ileal conduit between 2006 and 2010. Postoperative cross-sectional imaging studies performed for routine oncologic followup (1,736) were evaluated for parastomal hernia, defined as radiographic evidence of protrusion of abdominal contents through the abdominal wall defect created by forming the stoma. Univariable and multivariable Cox regression analyses were used to determine clinical and surgical factors associated with parastomal hernia. RESULTS: Complete data were available for 386 patients with radiographic parastomal hernia occurring in 136. The risk of a parastomal hernia developing was 27% (95% CI 22, 33) and 48% (95% CI 42, 55) at 1 and 2 years, respectively. Clinical diagnosis of parastomal hernia was documented in 93 patients and 37 were symptomatic. Of 16 patients with clinical parastomal hernia referred for repair 8 had surgery. On multivariable analysis female gender (HR 2.25; 95% CI 1.58, 3.21; p<0.0001), higher body mass index (HR 1.08 per unit increase; 95% CI 1.05, 1.12; p<0.0001) and lower preoperative albumin (HR 0.43 per gm/dl; 95% CI 0.25, 0.75; p=0.003) were significantly associated with parastomal hernia. CONCLUSIONS: The overall risk of radiographic evidence of parastomal hernia approached 50% at 2 years. Female gender, higher body mass index and lower preoperative albumin were most associated with the development of parastomal hernia. Identifying those at greatest risk may allow for prospective surgical maneuvers at the time of initial surgery, such as placement of prophylactic mesh in selected patients, to prevent the occurrence of parastomal hernia.
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Cistectomía/efectos adversos , Cistostomía/efectos adversos , Hernia Ventral/epidemiología , Complicaciones Posoperatorias/epidemiología , Anciano , Cistectomía/métodos , Femenino , Estudios de Seguimiento , Hernia Ventral/diagnóstico por imagen , Humanos , Masculino , New York/epidemiología , Complicaciones Posoperatorias/diagnóstico por imagen , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
UNLABELLED: Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; p<0.001) and worse CSS (HR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. PATIENT SUMMARY: Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches.